Prognostic value of D-dimer to fibrinogen ratio for patients with acute myocardial infarction

Abstract

Objective

Myocardial infarction is a severe disease with high in-hospital mortality without aggressive clinical treatment. The study aims to evaluate prognostic worth of D-dimer-to-fibrinogen (FIB) ratio (DFR) for patients with acute myocardial infarction (AMI).

Methods

133 patients (65 (37, 93) years old) from our hospital (China) with AMI were enlisted from January 2017 to December 2019. Patients were assigned into the survivor and nonsurvivor group based on in-hospital outcomes. Receiver operating characteristics (ROC) and multivariate analysis were fulfilled to analyze the prognostic value of DFR.

Results

The degree of DFR in the nonsurvivor group was significantly higher than that in the survivor group (p < 0.05). Logistic regression analysis presented that DFR (hazard ratio (HR), 2.207; 95% confidence interval (CI), 1.050–4.640; p = 0.037) was independently related with in-hospital death. ROC demonstrated that the area under the curve (AUC) of DFR was = 0.808 (0.725–0.892) (sensitivity, 85.3%; specificity, 69.7%).

Conclusion

DFR might be a new independent predictor of in-hospital death for AMI patients. Further studies are needed to validate this preliminary finding.

Keywords

D-dimer fibrinogen in-hospital mortality myocardial infarction

Introduction

Acute myocardial infarction (AMI) is a severe disease with high morbidity and mortality worldwide.^1-3 There are millions of people suffering from acute ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI). With the development of technology, the mortality and morbidity have greatly reduced.⁴ However, mortality may be influenced by several variables, such as age, smoking or not, and accompanied by hypertension, diabetes mellitus (DM).⁵ Distinguishing high-risk AMI patients is important.

Acute myocardial infarction is a disease that related with inflammatory response and thrombosis, accompanying with increased inflammatory factors (C-reactive protein (CRP), D-dimer, platelet count (PLT) and fibrinogen (FIB).^6-10 However, the combination of markers have been confirmed to be more excellent than one single index. Investigation has showed that D-dimer – to - FIB ratio (DFR) has a positive correlation with adverse events in patients with heart failure.¹¹ Thus, the purpose of this investigation is to assess the performance of DFR for AMI patients.

Method

This retrospective investigation was to estimate the prognostic value of DFR for AMI patients. Patients (age≥18 years) diagnosed as AMI based on 2017 ESC Guidelines between January 2017 and December 2019 were selected.¹ Patients accompanied by incomplete data, onset-to-admission time >48 h, missing follow-up results or had received therapy affecting coagulation before admission were excluded. At last, 133 patients were included. In-hospital outcomes (death or not) were obtained from the medical records. Patients were assigned into the survivor and nonsurvivor group based on in-hospital outcomes. Receiver operating characteristics (ROC) and multivariate analysis were fulfilled to analyze the prognostic value of DFR. The study was given official approval by the first affiliated hospital of Nanjing medical university and kept in line with the Declaration of Helsinki and informed consents were waived (2021-SR-529).

Data

The clinical results such as demographic factors, cardiovascular adverse indexes, medical history, admission laboratory indicators, electrocardiographic, computed tomography (CT) data and in-hospital outcomes were collected.

Statistical analysis

All analysis was gone through by IBM SPSS Statistics 21 software (IBM Corp., Armonk, NY). Patient characteristics were illustrated as frequencies (n (%)) for categorical variables. Normally distributed continuous variables (mean and standard deviation) were compared by Student t test while abnormally distributed variables (median and range) were compared by the Mann–Whitney U test. Receiver operating characteristic (ROC) was employed to investigate the performance of DFR to predict in-hospital mortality. P < 0.05 was believed statistically significant.

Results

Characteristics

Among the 133 patients with AMI, 99 (74%) patients were assigned into the survivor group and 34 (26%) patients were assigned into the nonsurvivor group. The median age of whole patients was 65 years and the ratio of male to female was 3:1. There were 55.6%, 7.5% and 3.7% of the patients with hypertension, cerebral infarction and coronary heart disease (CAD) respectively (Table1).

Table 1.

Baseline characteristics of study patients.

Variables	Total group (N = 133)	Nonsurvivor (N = 34)	Survivor (N = 99)	p value
Gender (male/female),n	101/32	24/10	77/22	0.401
Median age (range), y	65 (37, 93)	74 (46, 93)	63 (37, 87)	<0.001
Smoking	53 (39.8)	9 (26.5)	44 (44.4)	0.066
Drinking	31 (23.3)	4 (11.8)	27 (27.3)	0.067
Hypertension, n	74 (55.6)	24 (70.6)	50 (50.5)	0.042
DM, n	45 (33.8)	14 (41.2)	31 (31.3)	0.298
Hyperlipidaemia, n	3 (2.3)	1 (2.9)	2 (2.0)	0.100
STEMI, n	112 (84.2)	32 (94.1)	80 (80.8)	0.067
Onset-to-admission time, h	16 (1, 48)	18 (1, 48)	15 (1, 48)	0.235
CI	10 (7.5)	4 (11.8)	6 (6.1)	0.009
Myocarditis	1 (0.8)	0 (0.0)	1 (1.0)	0.088
CAD	6 (4.5)	1 (2.9)	5 (5.1)	0.001
CTNT	778.8 (6.22, 10000)	1692.5 (26.31, 10000)	593.4 (6.22, 10000)	0.002
PT (s)	12.75 ± 1.86	13.86 ± 2.83	12.37 ± 1.17	0.005
INR	1.11 ± 0.17	1.21 ± 0.258	1.08 ± 0.108	0.005
APTT (s)	28.2 (17.5, 180)	31.25 (23.4, 180)	27.9 (17.5, 147)	0.002
FIB (g/L)	3.78 ± 1.67	3.80 ± 1.73	3.77 ± 1.65	0.925
TT (s)	17.8 (15.2, 160)	18.0 (15.8, 160)	17.7 (15.2, 160)	0.379
D-dimer (mg/L)	0.60 (0.1, 17.38)	1.62 (0.1, 17.38)	0.41 (0.1, 13.81)	<0.001
WBC (×109/L)	9.81 ± 4.47	11.23 ± 5.57	9.32 ± 3.95	0.072
Lymphocyte (×109/L)	1.45 ± 0.67	1.34 ± 0.811	1.48 ± 0.618	0.301
Neutrophil (×109/L)	7.67 ± 4.29	9.14 ± 5.16	7.16 ± 3.85	0.058
HB (g/L)	129.36 ± 25.94	120.62 ± 22.17	132.36 ± 26.56	0.014
PLT (×109/L)	197.55 ± 67.63	182.68 ± 70.75	202.66 ± 66.12	0.154
ALT (U/L)	39.3 (7.3, 2024.5	46.45 (7.3, 2024.5)	36.6 (11.2, 204.4)	0.084
AST (U/L)	53.9 (9.5, 2788.1)	111.10 (15.6, 2788.1)	49.4 (9.5, 1361.4)	0.004
UREA (mmol/L)	6.4 (2.09, 53.82)	8.88 (4.18, 53.82)	5.99 (2.09, 42.89)	<0.001
CREA (mmol/L)	76.4 (33, 982.2)	105.85 (50.2, 982.2)	73.10 (33, 686.8)	0.003
DFR	0.16 (0.02, 1 1.0)	0.4 (0.04, 11.0)	0.12 (0.02, 3.63)	<0.001
Aspirin	90 (67.7)	15 (44.1)	75 (75.8)	0.001
PCI	128 (96.2)	31 (91.2)	97 (98.0)	0.073

Data are presented as mean±SD, median (range), or number of patients (n(%))

ALT: Alanine aminotransferase; APTT: Activated partial thromboplastin time; AST: Aspartate aminotransferase; CAD: Coronary heart disease; CI: Cerebral infarction; CREA: Creatinine; CTNT: Troponin T; DFR: D-dimer to FIB ratio; DM: Diabetes mellitus; FIB: Fibrinogen; HB: Hemoglobin; INR: International normalized ratio; PCI: Percutaneous coronary intervention; PLT: Platelet count; PT: Prothrombin time; TT: Thrombin time; UREA: Urea nitrogen; WBC: White blood cell count.

Comparison of variables between the two groups

No remarkable difference was noticed in the clinical data (include FIB, thrombin time (TT), white blood cell count (WBC), lymphocyte, neutrophil, PLT, alanine aminotransferase (ALT)) between the two groups (all p > 0.05); Elevated hemoglobin (HB) was observed in the survivor group; While coagulation indexes (except FIB), aspartate aminotransferase (AST), kidney function indicators, Troponin T (CTNT), DFR in the survivor patients were significant lower than that in nonsurvivor patients (all p < 0.05) (Table 1).

Indexes for in-hospital mortality

We involved these biomarkers in Table 1 with p < 0.05 into a model. Multivariate logistic regression analysis illustrated that these admission biomarkers were independently related with in-hospital death: Age (hazard ratio (HR), 1.095; 95% confidence interval (CI), 1.039–1.154; p = 0.001), cTNT (HR, 1.000; 95% CI, 1.000–1.001; p < 0.001), UREA (HR, 1.061; 95% CI, 1.001–1.125; p = 0.047), DFR (HR, 2.207; 95% CI, 1.050–4.640; p = 0.037) (Table 2).

Table 2.

Multivariate analysis for in-hospital death.

Variables	Multivariate analysis
Variables	HR	95%Cl	p value
DFR	2.207	1.050–4.640	0.037
UREA	1.061	1.001–1.125	0.047
CTNT	1.000	1.000–1.001	<0.001
Age	1.095	1.039–1.154	0.001

CI: Confidence interval; CTNT: Troponin T; DFR: D-dimer to FIB ratio; HR: Hazard ratio; UREA: Urea nitrogen.

In addition, AUC of biomarkers were presented as follows: AUC _Age= 0.731 (0.628–0.834) (sensitivity, 70.6%; specificity, 66.7%), AUC _CTNT = 0.678 (0.567–0.789) (sensitivity, 52.9%; specificity, 77.8%), AUC _UREA= 0.741 (0.645–0.838) (sensitivity, 70.6%; specificity, 74.7%), and AUC _DFR= 0.808 (0.725–0.892) (sensitivity, 85.3%; specificity, 69.7%) (Figure 1).

Figure 1.

The capability of independent factors in AMI patients in-hospital death.

Discussion

The most common performance of AMI is chest pain, while chest pain is not specific. It is reported that finally 1 in 10 coronary syndrome patients accompanied by chest pain are confirmed with MI.^12,13 Thus, effective, simple and available pathways are demanded to exclude patients with non-cardiac presentations and pick out those with AMI. Clinically, there is a lack of such indicators. Although the prognosis of patients with AMI has been significantly improved, AMI reserves a troublesome disease.^1,2,14 Thus, a novel biomarker with high sensitivity and specificity is claimed to appraise patients at risk at admission.

D-dimer is produced by the degradation of cross-linked fibrin by fibrinolytic enzyme.¹⁵ Significantly elevated D-dimer was seen many diseases such as aortic dissection, pulmonary embolism, myocardial infarction, disseminated intravascular coagulation, tumors, and sepsis.¹⁶ The capability of D-dimer is also reflected on the identification and prognosis of MI.^17,18 The performance of D-dimer is also reflected in this research.

Fibrinogen, a soluble glycoprotein, coming from hepatocytes, acted as an acute-phase protein and inflammation indicator.^19,20 Elevated FIB have been informed in many diseases such as cardiovascular disease and bladder cancer.^20,21 In addition, FIB has been reported to be related with artery disease even adjusted by confounding parameters.^22,23 However, in this study, we did not find the discrepancy in FIB.

Research presented the performance of a combination of two or more factors is better than that of one or a single factor alone. In this study, we confirmed this. A novel index named DFR was developed based on D-dimer and FIB. We found that DFR could be applied to predict in-hospital death even the confounding variables were adjusted. Apart from this, the AUC of DFR was higher than that of D-dimer and FIB alone. Patients with DFR > 0.1914 had a higher hazard of in-hospital death than patients with DFR ≤ 0.1914 group. These findings suggested that DFR can be employed to predict in-hospital death as an independent factor for AMI patients.

Finally, current study developed a simple risk prediction marker based on simple, rapid and cheap indexes in estimating the adventure of mortality in AMI patients. Physicians can quickly identify the high-risk of patients and make precision treatment with the help of this new indicator.

Limitations

Some limitations should be discussed. Firstly, as a single-center, retrospective cohort investigation, selection bias is unavoidable. Secondly, the number of selected patients was not big and the sample size was not calculated, which maybe underpowered to identify other forecast variables. Third, the analysis was developed on the value from the initial admission.

Conclusions

D-dimer-to-fibrinogen ratio might be a rapid, costless and helpful marker for predicting in-hospital mortality for AMI patients. Further studies are needed to validate this preliminary finding.

Footnotes

Author’s contribuitions

Jun Zhou and Min Wang designed the study. All the authors contributed to the generation, collection, assembly, analysis and/or interpretation of data. Litao Zhang wrote the manuscript. All the authors have revised and read manuscript and approved the final manuscript.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Ethics approval

The study was given official approval by the first affiliated hospital of Nanjing medical university and kept in line with the Declaration of Helsinki and informed consents were waived (2021-SR-529).

Informed consent

The study was given official approval by the Human Ethical Committee of the hospital and informed consents were waived (2021-SR-529).

Availability of data and materials

The datasets are accessible from the corresponding author on rational request.

ORCID iD

Jun Zhou

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